The project consists of two parts. In Part I, the aim is to determine how the genetic material interacts with the other constituents of the cellular environment to maintain both its loosely compacted structure when physiologically active and the densely compacted structure when inert. An approach to a hypothetical control mechanism based on this interchange is proposed using sedimentation analysis, electron microscopy, and the theory of interactions between macromolecules. Part II is concerned with the first steps in a program to detect molecular differences between homologous DNA of humans, with the ultimate hope of detecting and enumerating points of heterozygosity in an individual diploid genome and points of difference between any two individual genomes. Analysis of human DNA would permit the detection of genetic disease before birth and heterozygous carrier states in prospective parents, and also make feasible other presently impracticable investigations in human genetics, such as study of the dependence of degenerative disease on hereditary constitution. The first work will be the development of sensitive, very high resolution transport methods for separation and specific characterization of restriction enzyme fragments.